Systemic inflammatory response due to chloroform intoxication--an uncommon complication.

Well-known adverse effects of chloroform are drowsiness, nausea, and liver damage. Two cases with an uncommon complication due to chloroform intoxication are presented. In the first case, a general physician, because of nausea and dyspnea, admitted a 34-year-old woman to hospital. She developed a toxic pulmonary edema requiring mechanical ventilation for a few days, and a systemic inflammatory response syndrome (SIRS) with elevated white blood cell counts, a moderate increase of C-reactive protein, and slightly elevated procalcitonin levels. There were inflammatory altered skin areas progressing to necrosis later on. However, bacteria could be detected neither in blood culture nor in urine. Traces of chloroform were determined from a blood sample, which was taken 8 h after admission. Later, the husband confessed to the police having injected her chloroform and put a kerchief soaked with chloroform over her nose and mouth. In the second case, a 50-year-old man ingested chloroform in a suicidal attempt. He was found unconscious in his house and referred to a hospital. In the following days, he developed SIRS without growth of bacteria in multiple blood cultures. He died several days after admission due to multi-organ failure. SIRS in response to chloroform is a rare but severe complication clinically mimicking bacterial-induced sepsis. The mechanisms leading to systemic inflammation after chloroform intoxication are currently unclear. Possibly, chloroform and/or its derivates may interact with pattern recognition receptors and activate the same pro-inflammatory mediators (cytokines, interleukins, prostaglandins, leukotrienes) that cause SIRS in bacterial sepsis.

A regression model applied to gender-specific ethanol elimination rates from blood and breath measurements in non-alcoholics.

As elimination rates for alcohol are suggested to be gender specific, a novel regression model has been applied to estimate these rates for both men and women using experimentally measured data from 81 female and 96 male volunteers described in previous papers. Breath alcohol measurements were done with the Alcotest 7110 Evidential device and were coupled with concomitant sampling of venous blood. Statistical analyses involved use of a mixed linear model for blood alcohol concentration (BAC) and breath alcohol concentration (BrAC), respectively. The model takes regression lines for each test subject into account with an individual starting value (2 h after the end of drinking) and with an individual alcohol elimination rate per hour (coincidental effects). Further, the data was modeled so that an average alcohol elimination rate per hour could be estimated separately for both genders (constant effects). This enables us to methodically correctly estimate the back calculation. The elimination rates beta (60), which can be used for minimum and maximum back calculations for the BAC, were 0.115 g/kg/h and 0.260 g/kg/h, respectively, for women and 0.096 g/kg/h and 0.241 g/kg/h, respectively, for men. These figures widely deviate from gender-unspecific values commonly used in Germany (0.1 and 0.2 g/kg/h, respectively). The corresponding values for the BrAC were 0.061 mg/l/h and 0.124 mg/l/h for women and 0.049 mg/l/h and 0.112 mg/l/h for men. The probability of an over- or underestimation of the abovementioned extreme values is 0.3% in each case.

The influence of sex hormones on the elimination kinetics of ethanol.

The goal of the investigation was to research the influence of sex hormones on the elimination kinetics of ethanol. Forty-seven healthy men (average age 25+/-6.1 years) and 61 healthy women (average age 24+/-2.4 years) received 0.79-0.95g of ethanol/kg body weight in the form of an alcohol beverage of their choice. The target concentration for both sexes was a blood alcohol concentration (BAC) of 1.10g/kg. Blood samples for the determination of the ethanol concentration followed in the elimination phase in 10-20min intervals. The sex hormone levels (estradiol, progesterone and testosterone) were determined concomitantly from the serum. In men, the mean testosterone concentration was 5.3+/-1.6ng/ml, the mean estradiol concentration was 34.6+/-13.6pg/ml and the mean progesterone concentration was 0.9+/-0.3ng/ml. In women, the mean estradiol concentration was 47.6+/-52.6pg/ml and the mean testosterone concentration was 0.8+/-0.4ng/ml. Progesterone displayed a so-called dummy effect in women. In the high progesterone group (n=11), the mean concentration was 11.1+/-3.5ng/ml and in the low progesterone group (n=50) the mean was 0.6+/-0.3ng/ml. The mean hourly elimination rate (beta60) was 0.1677+/-0.0311g/kg/h in men. In women, the mean hourly elimination rate was 0.2044+/-0.0414g/kg/h in the high progesterone group and 0.1850+/-0.0276g/kg/h in the low progesterone group (p<0.05). The beta60 for women in the low progesterone group was significantly higher than that of the men, whose progesterone levels fell within a similar range (p>0.01). These results allow one to conclude that the gender differences in the pharmacokinetics of ethanol can partly, but not completely, be explained by progesterone levels.

Absinthe: attention performance and mood under the influence of thujone.

OBJECTIVE: The aim of this study was to determine whether the impacts of absinthe on attention performance and mood were different from those experienced with beverages that contain only alcohol. The ingredient causing absinthe's toxicity is believed to be thujone. METHOD: A total of 25 healthy subjects participated in the study. An attention performance test and two questionnaires testing different mood dimensions were used. Three drinks with an identical amount of alcohol but with different amounts of thujone were offered. RESULTS: The results of the present study showed that the simultaneous administration of alcohol containing a high concentration of thujone had a negative effect on attention performance. Under this condition, the subjects tended to direct their attention to signals in the central field of attention and to neglect peripheral signals; the number of correct reactions decreased significantly in the peripheral field of attention, and reaction time and the number of "false alarm" reactions increased significantly. The effects were most prominent at the time of the first measurement. When the subjects were under the influence of alcohol or were administered both alcohol and a low thujone concentration, these effects were not observed. The assessment of mood state dimensions showed that the anxiolytic effect of alcohol was temporarily counteracted by a high thujone concentration. CONCLUSIONS: As they are apparently opposed to the effect of alcohol, the reactions observed here can be explained by the antagonistic effect of thujone on the gamma-aminobutyric acid receptor. Similar alterations were observed for the other mood state dimensions examined.

Concentration dependency of the BAC/BrAC (blood alcohol concentration/breath alcohol concentration) conversion factor during the linear elimination phase.

According to the theoretical pharmacokinetical considerations put forward by Wehner et al. the BAC(ven)/BrAC conversion factor Q is not a constant value and varies depending on the pharmacokinetic phase deduced from the alcohol concentration curve. Based on these considerations we propose that Q must be inversely proportional to the BrAC during the postabsorptive linear elimination phase, expressed as the hyperbola Q=1/kappa+(CT)/BrAC. The constants kappa or 1/kappa and (CT)--where (CT) consists of different parameters which remain constant during the linear elimination phase--can be experimentally determined from the linear relationship BrAC = kappaBAC(ven)-kappa(CT). To test this hypothesis 12 human volunteers received parenteral doses of ethanol. During the elimination phase, BAC and BrAC of each volunteer were measured between 18 and 34 times in a BrAC range between 0.65 mg/l and 0.12 mg/l. The conversion factor Q was either expressed in the form of the hyperbola Q=1/kappa+(CT)/BrAC or directly calculated from the ratio BAC(ven)/BrAC and the results obtained using both methods were found to be very similar. The values of 1/kappa of the hyperbolic functions varied between 1.808 and 2.165 and those of (CT) between 0.004 and 0.127. For a BrAC of 0.25 mg/l, an average value of 2.308+/-0.080 could be calculated for the conversion factor Q(0.25). On average, the value of Q(0.40) amounted to 2.207+/-0.048 and that of Q(0.55) to 2.160+/-0.056.

Criteria for homicide and suicide on victims of extended suicide due to sharp force injury.

This report is about the findings in association with the extended suicides of nine victims killed by sharp force. All victims were killed by sharp force. The perpetrators were predominantly the parents, the victims their children. Regarding the criteria for differentiating self-inflicted injuries from injuries inflicted by another person, the victims' injuries presented patterns usually found solely in suicides. Thus eight of nine cases presented tentative and hesitation injuries, in three of five cases areas of injury covered by clothing had been exposed beforehand. Despite extremely narrow intercostal spaces in children, injuries to the bones in thoracic stabbing were avoided more often than not (four of seven cases). Only the criterion "defence injury" occurred nearly as often as in homicide victims (three of nine cases). The psychopathology of extended suicide can explain this pattern. The perpetrator's motive is characterised by his pseudoaltruistic belief to save the loved ones from a world that is in his opinion unacceptable. A fusion or integration of the victim into the perpetrator's own self is based on an identity problem. Physical interrelation of forces between perpetrator and victim restricts the victim in his defence and presents an important prerequisite for acquiring the patterns of described injuries.

Clodronate inhibits adrenocortical cell proliferation and P450c21 activity.

Bisphosphonates (BPs), specific inhibitors of osteoclasts, are well established in the management of skeletal metastases in breast cancer. Recent studies have suggested that these compounds may also directly influence tumor cell proliferation. As adrenocortical cancer frequently leads to bone metastases, we investigated the effects of clodronate (CLO) in the human adrenocortical cancer cell line NCI-H295 and in primary cultures of bovine adrenocortical cells. Both the non-amino BP CLO and the amino BP pamidronate (PAM) exhibited a dose-dependent antiproliferative effect in both cell types (cell viability in NCI-H295 cells: 100 microM CLO: 98+/-8%; 500 microM CLO 76+/-6%; 1000 microM CLO 53+/-2; 10 microM PAM 96+/-3%; 50 microM PAM 46+/-6%; 100 microM PAM 11+/-1% vs untreated control cells: 100+/-10%; P<0.01). FACS analysis in NCI-H295 cells treated with either CLO or PAM demonstrated both apoptotic and necrotic cell death. However, while during PAM treatment cell number and hormone secretion decreased in parallel, we observed specific impairment of steroidogenesis in the presence of CLO with a dose-dependent increase in the 17-OH-progesterone/cortisol ratio (100 microM CLO 134+/-30%; 500 microM CLO 284+/-10%; 1000 microM CLO 545+/-130% vs 100+/-20% in control cells; P<0.01). Further analysis in ACTH-stimulated bovine adrenal cells using stable isotope dilution/gas chromatography-mass spectrometry demonstrated CLO-induced inhibition of adrenal 21-hydroxylase (P450c21) activity leading to a dose-dependent increase in the 17-OH-progesterone/11-deoxycortisol ratio. In conclusion, we demonstrate a dose-dependent antiproliferative effect of CLO and PAM in adrenocortical cells. In addition, for the first time, we describe a suppressive effect of CLO on steroidogenesis via inhibition of adrenal 21-hydroxylase (P450c21) activity.

[Animal bites caused by a song bird?]. / Tierfrass durch einen Singvogel?

The report describes a case of post-mortem scavenging by a songbird. A married couple had opened the cage of an astrild (finch) prior to their joint death. The body of the wife showed unusual patchy epidermal lesions on parts of the body not covered by the clothing, which were obviously caused by the songbird. According to the observations made by Roll and Rous they are attributable to "pecking and pulling". The behaviour of the bird was most probably due to lack of fluid.

Quality of care and temperament determine changes in cortisol concentrations over the day for young children in childcare.

The current study investigated whether patterns of cortisol production in preschool-aged children in group care were influenced by characteristics such as group size, adult:child ratio, separation from family/parents, and quality of attention and stimulation from the childcare provider. Data were obtained from preschoolers attending home-based childcare. Cortisol levels were sampled at home and at childcare. Parents and teachers assessed the child's temperament (CBQ, TBQ). At childcare, the children were observed using the Observational Ratings of the Caregiving Environment (ORCE). Childcare characteristics were independent of family or child characteristics. In home-based childcare, children's cortisol patterns over the day correlated significantly with the amount of attention and stimulation provided by the childcare provider. Using a median split on the quality index measure of focused attention/stimulation, children in settings that were above the median exhibited no change in cortisol from home to childcare, while those in settings below the median exhibited a reversal of the typical pattern of cortisol production from morning to afternoon. At home these children exhibited the expected decrease in cortisol from morning to afternoon. Patterns of cortisol production at childcare were also correlated with child temperament with larger increases from morning to afternoon for more emotionally negative children and those with less self-control. Finally, cortisol production in home-based childcare was compared to data from children in center-based childcare and children not enrolled in full-day childcare.

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

OBJECTIVE: Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. DESIGN: Observational cohort study during two 12-day periods in successive years. SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of >50% and 2.5 nmol/L over the baseline. MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (>3 yrs of intensive care vs. <3 yrs, 4.1 vs. 4.95 nmol/L, p < .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with >8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p < .01). CONCLUSIONS: Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.

Objectifying psychomental stress in the workplace--an example.

BACKGROUND: Psychomental stress is a major source of illness and reduced productivity. Data objectifying physiological stress responses are scarce. We studied salivary cortisol levels in a highly stressful environment, the pediatric critical care unit. The aim was to identify targets for organizational changes, to implement these changes and to assess their impact on cortisol levels. DESIGN: Repeated measurements observational cohort study (before and after intervention). SUBJECTS: 84 nurses working in two independent teams (A and B) in a 19 bed pediatric intensive care unit. Between study periods team A experienced a major exchange of experienced staff while the turnover rate in team B remained average. MEASUREMENTS AND INTERVENTIONS: Salivary cortisol samples were collected every 2 h and after stressful events. Nurses in study period I showed elevated cortisol levels at the beginning of the late shift, interpreted as an anticipatory stress reaction. To ease conditions during the early part of the late shift (conflicting tasks, noise and crowding), we postponed the afternoon ward round, limited non-urgent procedures and introduced a change in visiting hours. The early shift, which was not affected by the intervention, served as control. MAIN RESULTS: Both crude and adjusted analysis revealed a decrease of cortisol levels at the beginning of the late shift in team B (p = 0.0009), but not in team A (p = 0.464). The control situation showed no difference between teams and study periods. INTERPRETATION: We demonstrated reduced cortisol secretions in one team following organizational changes, which was probably overridden by the disruption of social coherence in the second team.

Cortisol levels of young children in full-day childcare centers: relations with age and temperament.

Cortisol levels of 70 children, aged 39-106 months, were sampled at home and at their full-day childcare centers at two times of day, mid-morning and mid-afternoon. Parents and teachers completed questionnaires assessing child temperament (negative affectivity, surgency or extroversion, and effortful control) and aggressive behavior. The results replicated a previous study showing increases in cortisol levels over the day at childcare for preschool-aged children, while home levels followed the expected circadian decrease in cortisol from morning to afternoon for most children regardless of age. At childcare, 3- and 4-year olds were more likely to show elevations in cortisol by mid-afternoon than were older children. Controlling statistically for age, shyness for boys, and poor self-control and aggression for both sexes were associated with increases in cortisol over the day at childcare. The results suggest that younger children and those with more immature social skills may frequently experience elevations in cortisol as the day progresses in group care contexts.

Hormonal monitoring of age at sexual maturation in female Goeldi's monkeys (Callimico goeldii) in their family groups.

The aim of this study was to determine whether or not sexual maturation is attained in the family group in captive-born Goeldi's monkey (Callimico goeldii) and if so, at what age and body weight. To monitor ovarian activity in 14 female Goeldi's monkeys, urinary content of pregnanediol-3alpha-glucuronide (PdG) was determined using radioimmunoassay. Urinary samples were collected between the ages of 6 and 70 weeks. Subjects became sexually mature while still housed in their family groups, at a median age of 57 weeks (48-< 70 weeks). Median body weight at the age of sexual maturity was 473 g (N=10; 420-543 g). This corresponded to 90% of the median non-pregnant body weight of breeding females in our colony (526 g, N=8). Therefore, Goeldi's monkey is similar to Leontopithecus but different from Cebuella, Callithrix, and Saguinus, in terms of daughters ovulating in the family group and at a relatively young age.

Physiological Responses to parental separation and a strange situation are related to parental care received in juvenile Goeldi's monkeys (Callimico goeldii).

The relationship between parental care received and physiological and behavioral responses to parental separation, isolation, and reunion was investigated in seven juvenile Goeldi's monkey living in their family groups. Physiological responses were measured non-invasively: the hypothalamic-pituitary-adrenal axis via urinary cortisol output and the autonomic nervous system via piloerection on the tail. Parent-infant aggression demonstrated high intergroup variation and predicted: (a) an increase in urinary cortisol output, r(s) = 0.86, p = 0.04, and duration of piloerection, r(s) = 0.71, p = 0.08, at initial separation-isolation; (b) adaptation of piloerection, r(s) = -0.89, p = 0.03, to repeated separation-isolation. Juvenile Goeldi's monkeys that had received high parental aggression were more physiologically responsive to separation; they also sought more contact with their mothers at reunion, rs = 0.93, p = 0.02. We propose that these data are consistent with the hypothesis that high emotional reactivity is related to insecure attachment to aggressive parents in this New world primate.

Effect of the menstrual cycle, oral contraception and pregnancy on forearm blood flow, venous distensibility and clotting factors.

Forearm blood flow, venous distensibility and various clotting factors were determined in 118 apparently healthy women (mean age 26 years), either during the menstrual cycle, or while taking a combined contraceptive (A) with high progestin:estrogen ratio (d-norgestrel 0.125 mg + ethinylestradiol 0.03 mg), or a sequential contraceptive (B) with low progestin: estrogen ratio (megestrol 0.1/1 mg + ethinylestradiol 0.1 mg), or in the 1st, 2nd and 3rd trimester of pregnancy. Venous distensibility in women taking contraceptive A was higher than in other women during the follicular phase of a normal menstrual cycle. Venous distensibility was not affected by contraceptive B. Blood flow and blood pressure remained unchanged by contraceptives A and B. Fibrinogen concentration was increased by both contraceptives, factor VII was either decreased (A) or unchanged (B), and factor X was either unchanged (A) or increased (B). The oral contraceptive with the high progestagen component appeared to increase venous capacitance and may induce venous stasis, whereas coagulability was particularly enhanced by the estrogen-type contraceptive. Pregnant women differed from women on oral contraceptives in regard to peripheral circulation; they showed a tremendous increase of blood flow with secondary vasodilation.